The vast human toll and financial burden that tobacco places on society is no longer in question, yet effective treatments for smoking cessation are still unavailable. Nicotine has been found to be one of the primary reinforcing agents in tobacco. There remain many unanswered questions about the physiological correlates of nicotine administration. The current proposal seeks to investigate the relationship between dopamine (Da) release in the nucleus accumbens (NAcc), a site commonly associated with reward, and operant conditioning, and nicotine self-administration (SA). The specific aims of the proposal are (1) to determine the effects of nicotine on Da release within the mesolimbic system, specifically in projections from the ventral tegmental area (VTA) to the NAcc shell, using a novel approach that combines in vivo microdialysis with a 24-hour unlimited access self-administration (SA) model, and (2) to investigate the effects on Da in the Nacc shell when a reward is strengthened (via varying the dose of nicotine) and also the contingency of the reward is altered (via changing the FR schedule).